Investigation of syphilis immunology and Treponema pallidum subsp. pallidum biology to improve clinical management and design a broadly protective vaccine: study protocol.

BACKGROUND: The syphilis epidemic continues to cause substantial morbidity and mortality worldwide, particularly in low- and middle-income countries, despite several recent disease control initiatives. Though our understanding of the pathogenesis of this disease and the biology of the syphilis agent, Treponema pallidum subsp. pallidum has improved over the last two decades, further research is necessary to improve clinical diagnosis and disease management protocols. Additionally, such research efforts could contribute to the identification of possible targets for the development of an effective vaccine to stem syphilis spread. METHODS: This study will recruit two cohorts of participants with active syphilis infection, one with de novo infection, one with repeat infection. Whole blood specimens will be collected from each study participant at baseline, 4, 12, 24, 36, and 48 weeks, to track specific markers of their immunological response, as well as to compare humoral reactivity to Treponema pallidum antigens between the two groups. Additionally, we will use serum specimens to look for unique cytokine patterns in participants with early syphilis. Oral and blood samples, as well as samples from any syphilitic lesions present, will also be collected to sequence any Treponema pallidum DNA found. DISCUSSION: By furthering our understanding of syphilis pathogenesis and human host immune response to Treponema pallidum, we will provide important data that will help in development of new point-of-care tests that could better identify active infection, leading to improved syphilis diagnosis and management. Findings could also contribute to vaccine development efforts.

High Lifetime Prevalence of Syphilis in Men Who Have Sex With Men and Transgender Women Versus Low Lifetime Prevalence in Female Sex Workers in Lima, Peru.

BACKGROUND: The syphilis epidemic continues to cause substantial morbidity worldwide and is worsening despite ongoing control efforts. Syphilis remains an important public health problem among 3 key populations: men who have sex with men (MSM), transgender women, and female sex workers. METHODS: We conducted a retrospective chart review of patients that received rapid point-of-care treponemal antibody tests from January 2019 to July 2019 in 4 sexually transmitted infection (STI) clinics in Lima, Peru. We assessed patient medical records for human immunodeficiency virus (HIV) infection, history of STIs, as well as sociodemographic and behavioral characteristics. Cross-sectional descriptive analyses were used to determine factors associated with treponemal positivity. RESULTS: We included 401 patient records in our analyses: 252 MSM, 31 transgender women, and 118 female sex workers. The overall median age of patients was 29.0 years (interquartile range, 24.0-36.0 years). Positivity on the treponemal test was 28.9% (95% confidence interval [CI], 24.3%-33.3%) overall, 37.7% (95% CI, 31.7%-44.0%) for MSM, 54.8% (95% CI, 36.0%-72.7%) for transgender women, and 3.4% (95% CI, 0.9%-8.5%) for female sex workers. In the bivariate analysis, treponemal positivity was also associated with receptive anal sex in the last 6 months in MSM (P < 0.01). Additionally, treponemal positivity increased with age (P = 0.0212) and varied by socioeconomic status (P < 0.01). Multivariate Least Absolute Shrinkage and Selection Operator logistic regression showed that treponemal positivity was highly associated with HIV coinfection (adjusted odds ratio, 5.42) and previous STI other than HIV or syphilis (adjusted odds ratio, 1.54). CONCLUSIONS: A review of the medical records of members of 3 key populations who had recently received a rapid point-of-care treponemal test in Lima, Peru, revealed that lifetime prevalence of syphilis was high among MSM and transgender women, but low among female sex workers. Those results may indicate a need for more frequent, regular testing among MSM and transgender women-possibly in conjunction with HIV testing, and appropriate treatment of those shown to be positive.